Multidimensional structural-functional coupling uncovers network dysregulation and predicts binge-eating severity in bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is a severe psychiatric disorder characterized by dysregulated eating behaviors and impaired cognitive-emotional control. Despite increasing recognition of brain network dysfunction in BN, the interplay between structural connectivity (SC) and functional connectivity (FC), termed SC-FC coupling, remains poorly understood. This study aimed to comprehensively characterize SC-FC coupling alterations in BN using multimodal neuroimaging and to evaluate the predictive value for disordered eating behaviors. METHODS: This study enrolled 79 patients with BN and 69 healthy controls who underwent high-resolution structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). Functional and structural connectomes were constructed using the Schaefer-400 atlas. SC-FC coupling was quantified using eight biologically grounded similarity and communication metrics. A multivariate linear modeling framework was applied to estimate region-specific coupling profiles. Group comparisons and ridge regression-based leave-one-out cross-validation were used to identify altered coupling and predict symptom severity. RESULTS: The global topological properties of the SC and FC networks were preserved in BN. However, patients exhibited significantly reduced degree centrality and nodal efficiency in the inferior frontal gyrus within the FC network. SC-FC coupling, quantified using the matching index (MI), showed widespread regional alterations in BN, particularly within the default mode, control, and attention networks. Seventeen brain parcels demonstrated significant group differences in MI-based coupling (false discovery rate (FDR)-corrected, p < 0.05), with both hypercoupling and hypocoupling observed. Findings were parcellation-robust (Glasser-360 replication; Dice = 0.93 vs. Schaefer-400). Moreover, coupling features moderately predicted binge-eating frequency (r = 0.24, p < 0.001), but not questionnaire-based emotional or behavioral scores. CONCLUSIONS: In BN, macroscale white-matter organization is preserved, yet focal prefrontal functional decentralization and widespread, parcellation-robust SC-FC coupling changes invisible to single-modality analyses were observed. Multidimensional SC-FC coupling provides a sensitive neurobiological marker that explains clinically relevant variance in binge-eating behavior, highlighting its potential as a target for personalized diagnosis and intervention in BN.